Exp Mol Med.  2007 Aug;39(4):477-482.

Regulation of cell growth by fatty acid-CoA ligase 4 in human hepatocellular carcinoma cells

• Sung YK
• Park MK
• Hong SH
• Hwang SY
• Kwack MH
• Kim JC
• Kim MK

Abstract

Fatty acid-CoA ligase 4 (FACL4) is a central enzyme controlling the unesterified free arachidonic acid (AA) level in cells and the free AA is known to induce apoptosis. We have recently reported that expression of FACL4 is upregulated in about 40% of human hepatocellular carcinoma (HCC) and 50% of HCC cell lines, suggesting that FACL4 may be involved in liver carcinogenesis. In this study, we investigated whether HCC cell growth is regulated by FACL4. Immunoblot analysis showed that SNU 398 cells express very low or no detectable level of FACL4. We, therefore, transfected the SNU 398 cells with FACL4 expression vector, and clones expressing FACL4 were pooled and analyzed. We found that forced expression of FACL4 in SNU 398 promotes the growth of cells. In addition, we observed that triacsin C, a FACL4 inhibitor, inhibits the growth of Hep 3B cell line which expresses high level of endogenous FACL4. We also found that the triacsin C-mediated growth inhibition in Hep 3B cells results from the induction of apoptosis with evidence of Bcl-2 reduction. Altogether, our data show that FACL4 affects HCC cell growth and suggest that modulation of FACL4 expression/activity is an approach for treatment of HCC.

Keyword

apoptosis; arachidonic acid; carcinoma, hepatocellular; long-chain-fatty-acid-CoA ligase; triacsin C

MeSH Terms

Apoptosis
Carcinoma, Hepatocellular/*enzymology/pathology
Cell Line, Tumor
Cell Proliferation
Coenzyme A Ligases/antagonists & inhibitors/*physiology
Humans
Liver Neoplasms/*enzymology/pathology
Proto-Oncogene Proteins c-bcl-2/metabolism
Triazenes/pharmacology